Department of Dermatology, Columbia University, College of Physicians & Surgeons, New York, NY, USA.
Exp Dermatol. 2013 Oct;22(10):644-9. doi: 10.1111/exd.12228.
Hairless (HR) is a nuclear protein with corepressor activity that is highly expressed in the skin and hair follicle. Mutations in Hairless lead to hair loss accompanied by the appearance of papules (atrichia with papular lesions), and similar phenotypes appear when the key polyamine enzymes ornithine decarboxylase (ODC) and spermidine/spermine N(1) -acetyltransferase (SSAT) are overexpressed. Both ODC and SSAT transgenic mice have elevated epidermal levels of putrescine, leading us to investigate the mechanistic link between putrescine and HR. We show here that HR and putrescine form a negative regulatory network, as epidermal ODC expression is elevated when HR is decreased and vice versa. We also show that the regulation of ODC by HR is dependent on the MYC superfamily of proteins, in particular MYC, MXI1 and MXD3. Furthermore, we found that elevated levels of putrescine lead to decreased HR expression, but that the SSAT-TG phenotype is distinct from that found when HR is mutated. Transcriptional microarray analysis of putrescine-treated primary human keratinocytes demonstrated differential regulation of genes involved in protein-protein interactions, nucleotide binding and transcription factor activity, suggesting that the putrescine-HR negative regulatory loop may have a large impact on epidermal homeostasis and hair follicle cycling.
无毛（HR）是一种具有核抑制活性的蛋白质，在皮肤和毛囊中高度表达。HR 突变导致毛发缺失，伴有丘疹出现（无发丘疹病变），而当关键多胺酶鸟氨酸脱羧酶（ODC）和精脒/精胺 N（1）-乙酰基转移酶（SSAT）过表达时，也会出现类似的表型。ODC 和 SSAT 转基因小鼠的表皮腐胺水平升高，这促使我们研究腐胺与 HR 之间的机制联系。我们在这里表明，HR 和腐胺形成负反馈调节网络，因为 HR 减少时表皮 ODC 表达升高，反之亦然。我们还表明，HR 对 ODC 的调节依赖于 MYC 超家族蛋白，特别是 MYC、MXI1 和 MXD3。此外，我们发现腐胺水平升高导致 HR 表达降低，但 HR 突变时的 SSAT-TG 表型与 HR 突变时的表型不同。腐胺处理的原代人角质形成细胞的转录微阵列分析表明，参与蛋白质-蛋白质相互作用、核苷酸结合和转录因子活性的基因受到差异调控，这表明腐胺-HR 负反馈环可能对表皮稳态和毛囊周期有很大影响。
